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  3. Fibroblast to macrophage-like cell transition in renal inflammatory injury through the MR/CSF1 pathway induced by aldosterone

Fibroblast to macrophage-like cell transition in renal inflammatory injury through the MR/CSF1 pathway induced by aldosterone

  • Life Sci. 2025 Jul 1:372:123627. doi: 10.1016/j.lfs.2025.123627.
Ruyan Lv 1,  Ziqian Liu 1,  Haixia Guo 1,  Boya Zhang 1,  Xuan Wang 1,  Yunsong Peng 2,  Yi Chang 3,  Fan Yang 3,  Yunzhao Xiong 3,  Juan Hao 2,  Xiaomeng Gao 1,  Xiangting Wang 3,  Qingyou Xu 4,  Tatsuo Shimosawa 5,  Panpan Qiang 6
Affiliations

Affiliations

  • 1 Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
  • 2 Shijiazhuang Hospital of Traditional Chinese Medicine, Shijiazhuang 050200, China.
  • 3 Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China.
  • 4 Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China. Electronic address: qingyouxu@hebcm.edu.cn.
  • 5 Department of Clinical Laboratory, School of Medicine, International University of Health and Welfare, Narita 286-8686, Japan. Electronic address: tshimo-tky@umin.ac.jp.
  • 6 Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang 050200, China; Institute of Integrative Medicine, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, China. Electronic address: qiangpanpan@hebcm.edu.cn.
PMID: 40216224 DOI: 10.1016/j.lfs.2025.123627
Abstract

Aims: Inflammatory injury promotes the chronic kidney disease (CKD) progression，with renal macrophage accumulation and proliferation of as typical manifestations of inflammatory injury. We aimed to verify fibroblast to macrophage-like cell transition as a new source of macrophages that participate in renal inflammatory injury.

Materials and methods: Wistar rats were divided into Sham, ALD (aldosterone infusion for 12 weeks), and ESA (aldosterone infusion and esaxerenone by diet for 12 weeks) groups. Rat kidney interstitial fibroblast (RKF) were cultured, induced with aldosterone or CSF1, and treated with antagonists in vitro. The proportions of FSP-1+ F4/80+ cells in the rat kidney and RKF, including M1 marker iNOS/CD86 and M2 marker CD206/CD163 were assessed by flow cytometry and immunofluorescence staining. Single-cell RNA Sequencing was used to assess the origin of macrophages in the rat kidneys and related gene expression. Additionally, immunofluorescence was used to detect FSP-1+ F4/80+ cells in kidney biopsy samples from CKD patients.

Key findings: Fibroblast to macrophage-like cell transition was observed in both the kidneys of aldosterone-infused rats and in vitro aldosterone-treated RKF, with a predominant differentiation into the M1 phenotype. This transformation was mediated through the MR/CSF1 signalling pathway, revealing a novel source of macrophages and providing significant insights into the mechanisms underlying organ fibrosis.

Significance: Aldosterone induces fibroblast to macrophage-like cell transition through the MR/ CSF1 pathway.

Keywords

Aldosterone; CSF1; Fibroblast; Macrophage-like cell; Mineralocorticoid receptor.

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